Management of Asthma in School age Children On Therapy (MASCOT): a randomised, double-blind, placebo-controlled, parallel study of efficacy and safety

BackgroundAsthma affects one in eight children in the UK. National management guidelines have been available for many years but, unlike in adults, studies in children have been few, with their methodologies often based on inappropriate adult models. Sound medical evidence in support of the national guidelines for asthma management in children is lacking. The MASCOT study has been developed to address this need.ObjectivesTo determine whether adding salmeterol or montelukast to low-dose inhaled corticosteroids (ICSs) can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma.DesignA randomised, double-blind, placebo-controlled trial with a 4-week run-in period on a fluticasone propionate inhaler (100 μg twice daily) with inhaler technique correction. Patients who met the post run-in period eligibility criteria were randomised in the ratio of 1 : 1 : 1 and were followed for 48 weeks.SettingSecondary care hospitals based in England and Scotland with recruitment from primary and secondary care.ParticipantsChildren aged 6–14 years with asthma requiring frequent short-acting beta-2 agonist relief, with symptoms of asthma resulting in nocturnal wakening and/or asthma that has interfered with usual activities.InterventionsThree groups were compared: (1) inhaled fluticasone propionate 100 μg twice daily plus placebo tablet once daily; (2) inhaled fluticasone propionate 100 μg and salmeterol 50 μg twice daily (combination inhaler) plus placebo tablet once daily; and (3) inhaled fluticasone propionate 100 μg twice daily plus montelukast 5-mg tablet once daily.Main outcome measuresThe primary outcome was the number of exacerbations requiring treatment with oral corticosteroids over 48 weeks. Secondary outcome measures included quality of life as measured by the Paediatric Asthma Quality of Life Questionnaire with Standardised Activities [PAQLQ(S)] and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ); time from randomisation to first exacerbation requiring treatment with a short course of oral corticosteroids; school attendance; hospital admissions; amount of rescue beta-2 agonist therapy prescribed; time from randomisation to treatment withdrawal (because of lack of efficacy or side effects); lung function at 48 weeks (as assessed by spirometry); cost-effectiveness; adverse events.ResultsThe study was closed prematurely because of poor recruitment and the target sample size of 450 was not achieved. In total, 898 children were screened to enter the trial, 166 were registered for the 4-week run-in period and 63 were randomised (group 1: 19, group 2: 23, group 3: 21), with 38 contributing data for the primary outcome analysis. There were no significant differences between groups for any of the outcomes. Adverse events were similar between the groups except for nervous system disorders, which were more frequently reported on fluticasone plus montelukast.ConclusionsBased on the results of the MASCOT study it is not possible to conclude whether adding salmeterol or montelukast to ICSs can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma.Trial registrationCurrent Controlled Trials ISRCTN03556343.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 17, No. 4. See the HTA programme website for further project information.